RESEARCH ARTICLE Open Access

Synthesis of moxifloxacin–Au (III) and Ag (I)metal complexes and their biologicalactivitiesKondaiah Seku1*, Anil Kumar Yamala2, Mahesh Kancherla3, Kishore Kumar K4 and Vijayakumar Badathala3

Abstract

Background: The drug-metal complexes are used to control the growth of pathogens and parasites which areharmful to humans. Moxifloxacin (MOX) is a new fourth generation 8- methoxy fluoroquinolone. Its chemical nameis [1-cyclopropyl-7-(S,S)-2,8-diazabicyclo(4.3.0)- non-8-yl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinoline carboxylicacid hydrochloride]. Many researchers have reported Moxifloxacin-metal complexes with transition metals andstudied their biological applications. We have synthesized novel moxifloxacin- Au(III) and Ag(I) metal complexes([Au(MOX) 2 (Cl) 2 ].2H 2 O and [Ag (MOX) 2 ].2H 2 O), characterized, and found their biological activities.

Methods: Moxifloxacin- Au(III) and Ag(I) metal complexes were prepared by adding corresponding aqueoussolutions of Au(III) and Ag(I) metal salts to methanolic solution of Moxifloxacin. These metal complexes werecharacterized by physio-chemical techniques like UV-Vis, 1 H- NMR, FTIR, XRD, DSC, TGA, SEM and microanalyticaldata. The disc diffusion method was used to study the antibacterial activity of the Moxifloxacin-metal complexes.

Results: The structural assessment of these complexes has been carried out based on physio- chemical andspectroscopic methods. The powder X-ray diffraction data of the metal complexes revealed moderate crystallinity.SEM analysis confirms that [Ag(MOX) 2 ].2H 2 O complex has small rods like morphology whereas [Au(MOX) 2 (Cl) 2].2H 2 O has well crystalline rods like morphology. The results from DSC of moxifloxacin- Au(III) and Ag(I) metalcomplexes revealed the interaction between the drug and metals. Further, Au & Ag moxifloxacin metal complexeshave shown significant antibacterial activity against gram-positive and gram-negative bacteria.

Conclusions: The spectral and analytical results clearly confirmed the coordination chemistry of Au (III) and Ag (I)Moxifloxacin metal complexes. The IR, electronic transition and elemental data led to the conclusion that thegeometry of the complex of Au(III) is octahedral and that of Ag (I) complex is tetrahedral. The [Ag(MOX) 2 ].2H 2 Ocomplex has showed good antibacterial activity compared to [Au (MOX) 2 (Cl) 2 ].2H 2 O metal complex. Theantibacterial activity studies indicate the metal complexes have more biological activity than free ligand.

Keyword: Moxifloxacin-metal complexes, Gold, Silver, Structure, Biological activity

BackgroundNowadays, most of the metal ions play an important rolein many biological processes like biological function ofproteins, and operating many regulation, stabilization,completion courses of cellular functions. The use of goldmetal in complexation with drugs in modern, twentiethcentury medicine began with the discovery in 1890 by

the German bacteriologist Robert Koch that gold cyan-ide K [Au (CN)4] was bacteriostatic towards the tuberclebacillus. In 1920s, gold therapy was introduced for tu-berculosis. Gold drugs have been used to treat a varietyof diseases like psoriatic arthritis, a form of arthritis as-sociated with psoriasis, juvenile arthritis, palindromicrheumatism, and discoid lupus erythematosus. Encour-aging results have also been obtained with gold therapyas a treatment for various inflammatory skin disorderssuch as pemphigus, urticaria, and psoriasis (Thomas andPapandrea 1993).

* Correspondence: kondareddyseku@gmail.com1Department of Engineering, Applied Science-Chemistry, Shinas College ofTechnology, Shinas, Sultanate of OmanFull list of author information is available at the end of the article

Journal of Analytical Scienceand Technology

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Seku et al. Journal of Analytical Science and Technology (2018) 9:14 https://doi.org/10.1186/s40543-018-0147-z

Silver compounds have been used in external prepara-tions as an antiseptic, including both silver nitrate andsilver proteinate, which can be used in dilute solution aseye drops to prevent conjunctivitis in newborn babies.Silver nitrate is also sometimes used in dermatology insolid stick form as a caustic (“lunar caustic”) to treat cer-tain skin conditions, such as corns and warts. Addition-ally, silver nitrate is used in certain laboratory settings tostain cells (Lansdown 2006; Kokura et al. 2010). Silverhas also been used in cosmetics, intended to enhanceantimicrobial effects and the preservation of ingredients.Researchers had a significant interest in the utilization

of metal complexes as drugs to treat several humandiseases. Metal and metal-drug complexes medicinaluses and their applications are increasing clinically forcommercial importance. The preparation andcharacterization of the drug-metal complexes and evalu-ation (Sadeek et al. 2011; Power and Phillips 1993) ofthe biological activity have gained significance. Accord-ing to chelation theory, chelation enhances the biologicalactivity of metal complexes by increasing the complexity.Preparation of drug-metal complexes is of most signifi-cance in current days for curing of diseases by inhibitionof growth of pathogens. It is clear from the recentliterature that the trend towards the preparation ofthe drug-metal complexes has huge applications andwill continue to occur in future medicinal applications(Ott 2009; Gasser et al. 2011; Maftei et al. 2015;Simon et al. 2005). However, the newly prepareddrug-metal complexes have been more significant inpresent days, because they show good biological activityand these metal complexes find a role in detectingdiseases (Neda et al. 2000; Filimon et al. 2010). Thedrug-metal complexes were also used to control thegrowth of pathogens and parasites which are harmfulto humans.Moxifloxacin (MOX) is a new fourth generation

8-methoxy fluoroquinolone (Fig. 1). Its chemical name is[1-cyclopropyl-7-(S,S)-2,8-diazabicyclo(4.3.0)-non-8-yl-6--fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinoline carbox-ylic acid hydrochloride]. The drug was developed mainlyfor the treatment of community-acquired pneumonia andupper respiratory tract infections. Moxifloxacin is alsoused for the treatment of hospital-acquired infections andhas a very good safety and tolerability profile with trade

names Avelox, Avalox, and Avelon. Moxifloxacin is to beconsidered a drug of the last remedy when all other drugsare failed. It inhibits DNA gyrase, a topoisomerase IV, andtype II topoisomerase.The investigators are well-known with the preparation

of different metal complexes of moxifloxacin. W.F.El-Hawary et al. have reported spectrophotometric de-termination and biological activity of moxifloxacin.HCl.Sadeek et al. gave detailed study about the preparationand characterization of moxifloxacin metal complexesand their biological applications. Amina et al. have re-ported metal complexes of moxifloxacin–imidazolemixed ligands: characterization and biological studies.The majority of researchers reported about the prepar-ation and characterization of the moxifloxacin-metalcomplexes with transition metals and studied their bio-logical applications (Nakamoto et al. 1968; Soayed et al.2013; Sultana et al. 2014).However, reported literature has limited characteris-

tics and investigations in the moxifloxacin-metal com-plexes. These metal complexes were shown moderateactivity against gram-positive and negative bacteria.To our knowledge, no report is available in the litera-ture about the synthesis and characterization of noblemetal complexes of moxifloxacin. The development of

Table 1 UV-Vis spectra and magnetic moments of moxifloxacin–HCl and its complexes

Sample Electronic bands, λ, nm μeff Geometry

CTM–L π–π* n–π* d–d transitions

MOX.HCl 292 330 362 – – –

[Au(MOX)2(Cl2)].2H2O 298 335 365 – Paramagnetic Octahedral

[Ag(MOX)2]·2H2O 295 339 369 600–750 Paramagnetic Tetrahedral

*it idicates excitation

NH

H

NF

O

H3C

O

O

OH

H

HCl

Fig. 1 Structure of moxifloxacin HCl

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noble metal-based drugs with promising pharmaco-logical application may offer unique therapeutic op-portunities (Rafique et al. 2010). The inorganicchemistry is provided with better opportunities to usethe noble metal complexes (Mihorianu et al. 2016;Maftei et al. 2016a) as therapeutic agents on livingorganisms which is different from transition metalsand non-metals. The noble metal-drug complexeshave significant applications (Maftei et al. 2016b;

Neda et al. 1993a) in medicine and show a great di-versity in action.We report here synthesis and characterization of

novel moxifloxacin–Ag(I) and Au(III) metal complexes,[Au(MOX)2(Cl)2].2H2O and [Ag (MOX)2].2H2O. Thesynthesized moxifloxacin metal complexes were charac-terized by physio-chemical methods like UV-Vis,H1-NMR, FTIR, XRD, DSC, TGA, and SEM. Antibac-terial activity studies were carried out against

Fig. 2 FTIR spectra of a moxifloxacin–HCl, b [Au(MOX)2(Cl2)].2H2O, and c [Ag(MOX)2]·2H2O

Fig. 3 1H-NMR spectrum of moxifloxacin–HCl

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Fig. 4 1H-NMR spectrum of moxifloxacin–Ag(I) metal complex

Fig. 5 1H-NMR spectrum of moxifloxacin–Au(III) metal complex

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gram-positive and gram-negative bacteria for the pre-pared moxifloxacin metal complexes.

MethodsMaterialsMoxifloxacin and gold(III) chloride were purchased fromthe Sigma-Aldrich Limited, India. Silver nitrate, methanol,and ether were purchased from MERK, India. All the che-micals and reagents are analytical reagent grade and wereused without further purification. All glassware and mag-netic stir bars were cleaned in an aquaregia solution (3HCl:HNO3) and then cleaned with double distilled (DD) water.

Procedure for synthesis of Au (III) moxifloxacin metalcomplexIt was prepared by adding 1.6 g (0.01 M) amount ofmoxifloxacin ligand in 30 ml of methanol to the Au (III)ion (0.005 M) in distilled water and stirred about 12 h at50 °C and cooled to room temperature. Yellow colorprecipitate of the metal complex was obtained with goodyield. The precipitate was filtered and washed with hotwater followed by cold methanol to free from unreactedmetal salts and ligand. Finally, the residue was washedwith ether and dried in a desiccator.

Moxifloxacin HClIR (KBr, cm−1): 3530 (O–H stretching of HOH; COOH),3156 (aromatic C–H stretching), 2978, 2800 (aliphaticC–H stretchings), 1709 (C=O stretching; COOH), 1620(N–H bending), 1592, 1533 (aromatic C–C stretching),1490 (C=C stretching), 1422, 1323 (aliphatic C–H bend-ing), 1245 (C–F stretching), 1184 (C–O stretching), 1166(C–N stretching), 1111 (C–C stretching), 1016, 991 (C–Hbending; phenyl). 1H NMR (DMSO) ppm: δ 10.87(s,2H;NH2

+), 9.03 (s,1H;COOH), 8.78 (s,1H;Ar–CH–),7.81, 7.77 (s,1H, Ar–CH), 4.16, 4.14 (2H,H–2′,–CH2),4.07 (t,2H,H–4′,N–CH2), δ3.85 (s,3H,–OCH3), δ 3.72

(m,2H,H–3′,–CH2), δ3.34 (t, 2H,H–1′,N–CH2), δ 2.98(s,1H, H–6′,N–CH–, diasterotopic), δ2.73(s,1H, H–7′,–CH–,diasteriotopic), 1.358 (t,1H,H–8′,–CH–), 1.088(t,2H,H–9′,–CH2), 0.934 (t,2H,H–10′–CH2).

Moxifloxacin–Au(III) complexYield: 75%; IR (KBr, cm−1): 3375 (O–H stretching), 3056(aromatic C–H stretching), 2955, 2885 (aliphatic C–Hstretchings), 1620 (N–H bending), 1525 (C=C stretch-ing;phenyl), 1462 (aromatic C=C stretching), 1420, 1321(aliphatic C–H bending), 1369 (N–H bending), 1325(C–F stretching), 1189 (C–O stretching), 1080 (C–Nstretching), 1049 (C–C stretching), 1031, 975 (C–Hbending;phenyl).

1H NMR (DMSO) δ ppm: 10.54 (s,2H;NH2+), 9.07

(s,1H;COOH), 8.78 (s,1H;Ar–CH–), 7.81, 7.77 (s,1H, Ar–CH), 4.16, 4.14 (2H,H–2′,–CH2), 4.07 (t,2H,H–4′,N–CH2), 3.85 (s,3H,–OCH3), 3.72 (m,2H,H–3′,–CH2), 3.34(t, 2H,H–1′,N–CH2), 2.98 (s,1H, H–6′,N–CH–,dias-terotopic), 2.73 (s,1H,H–7′,–CH–,diasteriotopic), 1.35(t,1H,H–8′,–CH–), 1.08 (t,2H,H–9′,–CH2), 0.93 (t,2H,H–10′–CH2).

Procedure for synthesis of Ag (I) moxifloxacin metalcomplexIt was prepared by adding required 1.6 g (0.01 M)amount of moxifloxacin ligand in 30 ml of methanol to

Fig. 6 X-ray diffraction of moxifloxacin–Ag (I) complex

Table 2 X-ray diffraction data of moxifloxacin–Ag (I) complex

S. no. d expt d calc 2θ expt 2θ calc h k l

1 3.476 3.467 26.701 25.869 110

2 2.924 2.833 27.91 30.574 111

3 2.704 2.452 32.34 33.619 002

4 2.036 2.002 46.24 45.257 211

5 1.692 1.733 54.83 53.754 013

6 1.605 1.634 57.53 56.428 113

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the Ag (I) ion (0.005 M) in distilled water and stirredabout 8 h. Light yellow color precipitate of the metalcomplex was obtained in good yield. The precipitate wasfiltered and washed with hot water followed by coldmethanol to free from unreacted metal salts and ligandand finally with ether and dried in a desiccator.

Moxifloxacin–Ag(I) complexYield: 80%; IR (KBr, cm−1): 3380 (O–H stretching), 3046(aromatic C–H stretching), 2953, 2880 (aliphatic C–Hstretchings), 1624 (N–H bending), 1516 (C=C stretching;phenyl), 1459 (aromatic C=C stretching), 1422, 1323 (ali-phatic C–H bending), 1376 (N–H bending), 1320 (C–Fstretching), 1185 (C–O stretching), 1084 (C–N stretch-ing), 1051 (C–C stretching), 1030, 965, 877 (C–H bend-ing;phenyl). 1H NMR (DMSO) δ ppm: 10.38(s,2H;NH2

+), 9.06 (s,1H;COOH), 8.78 (s,1H;Ar–CH–),7.80, 7.76 (s,1H, Ar–CH), 4.16, 4.14 (2H,H–2′,–CH2),4.07 (t,2H,H–4′,N–CH2), 3.85 (s,3H,–OCH3), 3.72(m,2H,H–3′,–CH2), 3.34 (t, 2H,H–1′,N–CH2), 2.93(s,1H, H–6′,N–CH–,diasterotopic), 2.73 (s,1H, H–7′,–CH–, diasteriotopic), 1.35 (t,1H,H–8′,–CH–), 1.08(t,2H,H–9′,–CH2), 0.93 (t,2H,H–10′–CH2).

CharacterizationThe characterization of the synthesized moxifloxacinligand and its metal complexes were recorded withUV-Vis-NIR spectrophotometer (UV-3600, Schimadzu)at 200–700 nm. FTIR analysis was carried out by KBrpellet method using JASCO FTIR 4600 in the scanningrange of 450–4000 cm−1 used for recording spectrum.The powder XRD technique was used to study crystal-line nature of the AuNPs by XRD (Rigaku, Miniflex)method with Cu kα (λ = 1.5418 Å) radiation. Themorphology of the prepared moxifloxacin and its metal

complexes was examined by SEM. The 1H NMR spec-tra of the ligand and its metal complexes were recordedon an AV-400 MHz NMR spectrometer in IICT, Hy-derabad in DMSO-d6 and CDCl3 solvents at roomtemperature. Microanalysis data were obtained using aCarlo Erba EA1108 elemental analyzer. Thermogramswere obtained using Perkin Elmer DSC 4000 differen-tial scanning colorimeter at Vishnu Chemical, Hydera-bad, India. Melting points were determined on theKofler Hotstage microscope (Reichart Thermovar) andwere uncorrected.

Biological activity studiesThe disc diffusion method was used to study the anti-bacterial activity of moxifloxacin, and its gold(III) andsilver(I) metal complexes. B.Cereus, PseudomonasAuruginosa, B. Subtilis, and E. coli were used as modeltest strains. Prepared Luria-Bertani (LB) agar mediumwas transferred into sterilized Petri dishes and then so-lidified. Petri plates were spread with bacterial strainsin a laminar airflow hood. Using micropipette, 10, 20,30, and 40 μL of the AuNPs solution and 10 μL ofstreptomycin solutions were added to each well of all

Fig. 7 X-ray diffraction of moxifloxacin–Au(III) complex

Table 3 X-ray diffraction data of moxifloxacin–Au (III) complex

S. no. d expt d calc 2θ expt 2θ calc h k l

1 3.638 3.567 24.44 24.25 101

2 2.924 2.853 28.60 29.21 111

3 2.704 2.652 32.52 31.88 002

4 2.036 2.012 46.43 45.65 211

5 1.692 1.683 54.13 53.75 103

6 1.600 1.585 57.53 56.95 113

7 1.217 1.213 78.48 78.23 322

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plates. They were dried in the laminar hood and incu-bated 24 h at 37 °C. All bacterial zones of inhibitionwere measured and assay was performed in triplicate.

Results and discussionElectronic spectra and magnetic measurementsUV-Visible absorption spectral data of the moxifloxacinligand and its moxifloxacin–Au(III) and moxifloxacin–Ag(I) metal complexes were shown in Table 1. Theelectronic transition of the ligand occurred at 292 nm(Table 3). But on complexation with the different metalions like Au (III) and Ag (I), new bands appeared at299 and 295 nm, respectively corresponding to thetransitional charge transfer from the ligand to the dif-ferent metal ions. Bands occurred in the region of 295and 298 nm, respectively for [Ag(MOX)2]·2H2O and[Au(MOX)2(Cl2)].2H2O metal complexes (Sultana et al.2014; Kondaiah et al. 2017) are assigned to chargetransfer transition (L→M). The magnetic moments ofthe present moxifloxacin of Au (III) and Ag (I) com-plexes are 1.80 and 1.75 BM, respectively. The magneticmoments of these ranges are suggested octahedralgeometry for Au (III) and tetrahedral geometry for Ag

(I) complex (Kadyrov et al. 1996; Neda et al. 1996;Sonnenburg et al. 1994).

FTIR spectroscopic studiesThe IR spectra of moxifloxacin ligand and its Au (III)and Ag(I) metal complexes were recorded by FTIR spec-trophotometer (Kunze et al. 2002; Maftei et al. 2013;Neda et al. 1993b; Plinta et al. 1994). The FTIR spectraof the silver and gold complexes of moxifloxacin ligandexhibited major changes as compared to the free ligand.The strong bands at 1707 and 1624 cm−1 in thespectrum of moxifloxacin are assigned pyridone car-bonyl and carboxyl stretches. In the FTIR spectra of Au(III) and Ag(I) complexes, the band at 1707 cm−1 wasnot recorded due to the formation of a bond betweenthe metal ion and carboxylate oxygen (Fig. 2.) Two newbands are appeared for these complexes (Tulkens et al.2012; Muhammad et al. 2007), at 1624 and 1335 cm−1,1620 and 1329 cm−1, were assigned to asymmetric andsymmetric ʋ(COO), respectively, for Ag (I) and Au(III)–moxifloxacin metal complexes. The difference values[DV = ʋas(COO)–ʋs(COO)] of 289 and 290 for Au(III) andAg (I) complexes respectively are used as an evidence forthe bidentate chelation mode of the group. These results

a Moxifloxacin b [Ag(MOX)2].2H2O metal complex

c [Au(MOX)2(Cl)2].2H2O metal complex

Fig. 8 SEM images of a moxifloxacin, b [Ag(MOX)2].2H2O, and c [Au(MOX)2(Cl)2].2H2O metal complexes

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revealed that the chelation of metals on moxifloxacin inthis work.

1H NMR spectroscopic studiesThe proton NMR spectra of moxifloxacin Ag(I) andAu(III) metal complexes have been recorded in CDCl3and DMSO–d6 and compared to the spectrum ofmoxifloxacin (Fig. 3). The moxifloxacin ligand 1H NMRspectra, a broad singlet signal, were observed at δ10.87 ppm corresponding to (2H,NH2

+), and a strongsinglet signal appeared at δ 9.03 ppm corresponding to–COOH. The aromatic protons that are H-2 and H-5are very close to the coordination site of the moxifloxa-cin ligand. H-2 proton of moxifloxacin ligand appeared,strong singlet at δ 8.78 ppm and H-5 proton of moxi-floxacin ligand noticed at (δ 7.81, 7.77 ppm) and ap-peared as a doublet. A triplet at (δ 4.18, 4.16, 4.14 ppm)due to [2H,N–4′–CH2]. The H-1′and H-5′ protonswere observed as doublet signal at (δ 4.07, 4.02 ppm),i.e., [4H,(2N–CH2)], a singlet of 3H of OCH3 group ap-peared at δ 3.85 ppm. The spectral band of [1H,8′–H]was shown at δ 3.30 ppm, a triplet at [4H (δ 2.98, 2.91,2.73 ppm)] due to [4H (2H-2′, 2H-3′)] and (δ 1.28,1.29, 1.35 and 0.93, 0.87 ppm)] due to [4H, (2H-9′,2H-10′)]. Upon addition of a metal, these protonsundergo the most significant changes. In the metal

complexes, the H-2 proton gives a new signals at δ = 8.72and 8.62 ppm while H-5 proton signals were appeared atδ 7.76 and 7.81 ppm, respectively, for Au (III) and Ag (II)moxifloxacin metal complexes (Figs. 4 and 5) (Chiririwaand Muzenda 2014; Ali et al. 2013; Efthimiadou et al.2006). This shift is due to the complexation and differencein the configuration of complexes than ligand. In the 1HNMR spectrum, a signal observed at δ 9.03 ppm due tocarboxylic –OH proton in the ligand is shifted to δ 9.11and 9.07 ppm respectively for Au (III) and Ag (II) moxi-floxacin metal complexes.

Powder XRD studies of moxifloxacin metal complexesPowder XRD studies of moxifloxacin–Ag (I) metal complexThe XRD patterns are used to explain qualitatively thedegree of crystallinity. The diffractogram (6 diffractions)reflects between 20 and 80° (2θ) values (Fig. 6) for moxi-floxacin–Ag (I) complex. All the peaks have beenindexed 2θ values compared in the graph. On compari-son, the values reveal that there is a good agreement(Arayne et al. 2005; Turel 2002) between values of 2θand d values. The diffraction peaks observed at 2θ values26.71, 27.91, 32.22, 46.25, 54.84, and 57.53° were indexedas (110), (110), (111), (002), (211), (013), and 113, re-spectively, as shown in Fig. 6. The maximum orientationobserved at (002) at 2θ of 32.22 °. The formation of

Fig. 9 DSC thermogram of moxifloxacin–Ag (I) metal complex

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[Ag(MOX)2].2H2O metal complex was confirmed byX-ray diffraction technique. These results agreed wellwith the standards of the Joint Committee on powderdiffraction standards (JCPDS NO.01-072-0607). TheX-ray diffraction data of MOX–Ag (I) complex are pre-sented in Table 2. The powder X-ray diffraction datashowed identical features with moderate crystallinity(Drevensˇek et al. 2006).

Powder XRD studies of moxifloxacin–Au (III) metal complexThe XRD patterns are used to explain qualitatively thedegree of crystallinity. The diffractogram (6 diffractions)reflects between 20 and 80° (2θ) values (Fig. 7) for moxi-floxacin–Au (III) complex. All the peaks have been

indexed 2θ values compared in the graph. On compari-son, the values reveal that there is good agreement be-tween values of 2θ and d values. The diffraction peaksobserved at 2θ values 24.44, 28.601, 32.52, 46.43,54.13,57.53, and 78.48 ° were indexed as (101), (111), (002),(211), (103), (113), and (322), respectively, as shown inthe Fig. 7. The formation of [Au(MOX)2(Cl2)].2H2Ometal complex was confirmed by X-ray diffraction tech-nique (De Almeida et al. 2007). These results are in goodagreement with the standards of the Joint Committee onpowder diffraction standards (JCPDS no. 04-0784). TheX-ray diffraction data of MOX–Au(III) complex are pre-sented in Table 3. The powder X-ray diffraction datashowed moderate crystallinity.

Fig. 10 DSC thermogram of moxifloxacin–Au (III) metal complex

Table 4 Thermal analytical data of the moxifloxacin metal complexes

Complex Wt of the complex in mgs Stage Temp in range 0C Probable assignment Mass loss (%) Total loss (%)

[Au(MOX)2(Cl)2].2H2O 4.147 1 145–320 Loss of 2H2O and Cl2molecule 5.44 87

2 370 Loss of 2 L molecule 83.218

3 530 Corresponds to AuO 11.14

[Ag(MOX)2].2H2O 4.245 1 140–325 Loss of 2H2O and Cl2 molecule 5.404 88

2 490 Loss of 2 L molecule 78.816

3 500 Corresponds to AgO 15.64

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SEM analysisThe SEM micrographs (morphology) of the moxifloxacinHCl have been taken in different magnification. The moxi-floxacin HCl showed small needle-like morphology.[Ag(MOX)2].2H2O complex has shown small rods likestructure whereas [Au(MOX)2(Cl)2].2H2O showed wellcrystalline rod-like (Efthimiadou et al. 2008) structures(Fig. 8). The SEM micrographs of moxifloxacin metal com-plexes, [Au(MOX)2(Cl)2].2H2O and [Ag(MOX)2].2H2O, re-veal the structural modification, and it clearly indicates theformation of complexes.

Differential scanning colorimeterDSC thermograms have shown an endothermic peakof moxifloxacin pure drug at 238.35 °C, which corre-sponded to its melting point. DSC thermograms(Figs. 9 and 10) of moxifloxacin–Au(III) and moxi-floxacin–Ag(I) metal complex showed endothermicpeaks at 261 and 228.67 °C, respectively (Khairnarand Singh 2016). The results of the thermograms ob-tained from DSC of moxifloxacin–Au(III) and Ag(I)metal complexes revealed the interaction between thedrug and metals.

Thermal behavior of Au (III) and Ag (II) moxifloxacin metalcomplexesThe thermogravimetric studies of all the complexes werecarried out in the air at a heating rate of 10 °C per mi-nute. The thermoanalytical data are summarized inTable 4. The thermal decomposition of the complexesproceeds in three stages. Au (III) and Ag (I) complexesare thermally stable up to 132 and 138 °C, respectively.This table agreed with the elemental analysis of Table 5.The first stage of decomposition corresponds to endo-thermic dehydration of complexes by the loss of two

water molecules and chlorine occurs in the temperaturerange 145–320 and 140–325°C, respectively (Attimaradet al. 2012; Drevensˇek et al. 2006). The second decom-position with exothermic peak by the loss of ligand moi-ety occurs in the temperature at 490 and 492 °C,respectively. The solid residues above 530 and 500 °Cwere identified as Au and Ag metal oxides, respectively.In all the complexes, the final products are metal oxides(Chawla et al. 2012; Trindade et al. 2006).The molar conductance of complexes in DMF (~ 10–

3 M) was determined at 27 + 2 °C using systronic 303reading conductivity bridge for Au(III) and Ag (I) com-plexes of moxifloxacin. These complexes are highly sol-uble in dimethylformamide (DMF). Therefore, these metalchelates are dissolved in DMF to perform conductivitymeasurements (El-Megharbel et al. 2015; Kljun et al. 2011;Khairnar and Singh 2016). A known amount of solid com-plex was transferred into 25 ml standard flask and dis-solved in DMF. The contents were made up to the markwith DMF. The complex solution is transferred into aclean and dry 100 ml beaker. The molar conductancevalues of these metal complexes are measured and foundto be 4.30 and 4.40 for Au (III) and Ag (II) complexes, re-spectively. These values suggest non-electrolytic nature(Gobec et al. 2014) of the present complexes.The elemental analysis of moxifloxacin ligand and its

metal complexes also performed; the compositions of themetal ligands with percentages calculated and found weretabulated in Table 5. The colored solid MOX–HCl com-plexes were stable in the air and insoluble in H2O andmost organic solvents except for DMSO and DMF upongentle heating (Patel et al. 2011). The products were deter-mined as non-electrolytes. The structures of MOX–HClcomplexes were deduced as [Au(MOX)2(Cl)2].2H2O and[Ag(MOX)2].2H2O.

Table 5 Analytical data of the moxifloxacin ligands and its metal complexes

Compound Color Yield in % Meltingpoint in 0C

Elemental analysis

Carbon % Hydrogen % Nitrogen % Metal %

Calc. Found Calc. Found Calc. Found Calc. Found

MOX–HCl Yellow – 238–242 – 57.34 – 6.19 – 9.55 – –

[Au (MOX)2(Cl)2].2H2O Yellow 75 255–266 49.25 49.12 5.40 5.15 8.85 8.78 6.12 6.05

[Ag (MOX)2].2H2O Light yellow 80 242–250 46.39 46.10 5.44 5.20 10.21 10.05 15.05 14.95

Table 6 Antibacterial activities of moxifloxacin and its metal complexes

Complexes Staphylococcus aureus Bacillussubtillis

Streptococcus features Pseudomonas aereuguinosa Escherichiacoli

MOX–HCl 8.40 27.50 25.61 8.40 18.31

[Au (MOX)2(Cl)2].2H2O 14.30 12.11 10.15 13.50 15.45

[Ag (MOX)2].2H2O 15.24 17.16 15.20 15.20 25.65

Seku et al. Journal of Analytical Science and Technology (2018) 9:14 Page 10 of 13

Antibacterial activityThe antibacterial activity of the moxifloxacin drug and itsmetal complexes (as a standard moxifloxacin) was testedagainst bacteria because bacteria can achieve resistance toantibiotics through biochemical and morphological modi-fications (Sultana et al. 2014; Mihorianu et al. 2016; Mafteiet al. 2016a; Maftei et al. 2016b). The organisms used inthe present investigations included Staphylococcus aureus(S. aureus), Streptococcus features (S. features) and Bacillussubtillis (B. subtilis) (as gram-positive bacteria) andProteus mirabilis (P. mirabilis), Pseudomonas aereugui-nosa (P. aereuguinosa), and Escherichia coli (E. coli)(as gram-negative bacteria). The zone of inhibition ofmoxifloxacin and its metal complexes against gram-nega-tive and gram-positive bacteria were then evaluated by thewell diffusion method (De Almeida et al. 2007; Efthimia-dou et al. 2008; Patel et al. 2011; Singh et al. 2013; Tavareset al. 2004). The results of the bacterial screening of thesynthesized compounds were recorded as shown inTable 6. The bacterial inhibition clear zones of bothgram-positive and gram-negative bacteria can be observedaround the well, while the zone of inhibition of moxifloxa-cin was moderate compared to all the metal complexes.Antibacterial activity of all the metal complexes signifi-cantly increased compared to the standard moxifloxacin.In these, moxifloxacin–Ag (I) metal complexes showed in-creased antibacterial activity compared to Au–moxifloxa-cin metal complexes (Nabd El-Wahed et al. 2009).

ConclusionsIn this research work, novel Au(III) and Ag (I) moxifloxacinmetal complexes were synthesized and characterized bymagnetic susceptibility, elemental analysis, UV-Vis, FTIR,1H-NMR, TGA, DSC, and SEM. The spectral and analyticalresults clearly described the coordination chemistry of Au(III) and Ag (I) moxifloxacin metal complexes. The IR, elec-tronic transition, and elemental data lead to the conclusionthat the geometry of the complexes of Au(III) is octahedral

and that of Ag (I) complex is tetrahedral structure. Hence,the structures of moxifloxacin metal complexes are given inFig. 11. In all the complexes, the ligand acts as a bidentate.These metal complexes have shown significant antibacterialagainst the tested organisms. The [Ag (MOX)2].2H2Ocomplex showed good antibacterial activity compared to[Au (MOX)2(Cl)2].2H2O metal complex. The antibacterialactivity indicates the metal complexes have more biologicalactivity than free ligands. All the metal chelates are foundto be non-electrolytes. These results will definitely en-courage more research towards drug-metal complexesin medicine.

Abbreviations[Ag(MOX)2]·2H2O (II): Moxifloxacin–Ag(I)metal complex; [Au (MOX)2(Cl2)].2H2O(I): Moxifloxacin–Au(III)metal complex; 1H-NMR: Proton nuclear magneticresonance spectroscopy; DSC: Differential scanning colorimeter; FTIR: Fouriertransform infrared spectroscopy; MOX–HCl: Moxifloxacin hydrochloride;TGA: Thermo gravimetric analysis; UV-Vis: Ultra violet visible spectroscopy;XRD: X-ray diffraction studies; AAS: Antibacterial activity studies; MAD: Microanalytical data

AcknowledgementsThe first author would like to thank UGC, New Delhi, India for the financialsupport from UGC Minor Research Project Grant (Sanction letter no: F.MRP–6210/15(SERO/UGC). The author thanks the Principal and Management of MallaReddy Engineering College (Autonomous) for providing research facilities.

FundingUniversity Grants Commission (no: F.MRP–6210/15(SERO/UGC), Delhi, India.

Authors’ contributionsKS synthesized the moxifloxacin-silver and gold metal complexes. KS, MK, andVB characterized moxifloxacin and their metal complexes using FT-IR andH1NMR spectra. AY and KS characterized the moxifloxacin metal complexesusing X-ray diffraction and SEM. SK and VB characterized the moxifloxacin metalcomplexes using electronic spectra, DSC, elemental analysis, and TGA. KKKconducted antibacterial studies on moxifloxacin and their metal complexes.All authors read and approved the final manuscript.

Ethics approval and consent to participateNA

Consent for publicationNA

HNH

H

NF

O

H3C

O

O

O

NH

H

H

N

F

O

CH3

OO

O

Ag

.2HCl

.2H2O

a

HNH

H

NF

O

H3C

O

O

O

NH

H

H

N

F

O

CH3

OO

O

Au

.2HCl.2H2OCl

Cl

bFig. 11 Proposed structures of moxifloxacin metal complexes. a Moxifloxacin–Ag(I) metal complex and b moxifloxacin–Au(III) metal complex

Seku et al. Journal of Analytical Science and Technology (2018) 9:14 Page 11 of 13

Competing interestsThe authors declare that they have no competing interests.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in publishedmaps and institutional affiliations.

Author details1Department of Engineering, Applied Science-Chemistry, Shinas College ofTechnology, Shinas, Sultanate of Oman. 2Department of School ofEngineering Sciences and Technology, University of Hyderabad, Hyderabad,Telangana State, India. 3Department of Chemistry, Vel Tech High TechDr.Rangarajan Dr.Sakunthala Engineering College, Avadi, Chennai, India.4Department of Pharmaceutics, Narayana Pharmacy College, Nellore, AndhraPradesh State, India.

Received: 5 February 2018 Accepted: 19 June 2018

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